Steerable blood pressure control is of great importance in many acute clinical situations, e.g. in the majority of patients undergoing cardiac surgery, cerebral surgery , orthopedic surgery or microsurgery. Under such conditions it is often important to rapidly and safely lower blood pressure to a pre-specified level, keeping it there for a pre-determined time, and then rapidly normalizing it again.
Although some drugs are presently used in the clininc for such purpose, none of them are really adequate for efficient blood pressure control.
The drugs most commonly used for this indications are sodium nitroprusside, nitroglycerine and nicardipine. Sodium nitroprusside is an old, potent and very short-acting compound wich in most countries is the only drug available with a suitable profile of acion, i.e. mainly causing arterial dilation. However, several serious side effects limit its usefulness. The main disadvantage being the risk of cyanide intoxication. A second disadvantage is its effects on regional myocardial blood flow in patients with coronary artery disease. Nitroglycerine is also very short-acting, but has too low potency to be really effective except in high doses which also causes unwanted lowering of cardiac output. Nicardipine, which is a calcium antagonist of the dihydropyridine type, has high vascular selectivity and high potency, but the effect duration is too long, as usually is the case for this class of compounds.
Thus, there exist today a clear medical need for new short-acting, steerable antihypertensive drugs for intravenous administration. The compounds of the present invention are useful for this purpose.